Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise

E. A. Mokelke, Q. Hu, M. Song, L. Toro, H. K. Reddy, Michael Sturek

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Chronic hyperglycemia and hypercholesterolemia have been shown to alter ionic currents in vascular smooth muscle. We tested the hypothesis that the combined effect of hyperglycemia and hyperlipidemia (diabetic dyslipidemia) would increase the Ca2+-sensitive K+ (KCa) current as a compensatory response to an increase in intracellular Ca 2+ concentration. We also hypothesized that exercise training would prevent this elevation in KCa current. Miniature Yucatan swine were randomly assigned to five groups: control, standard pig chow (C, n = 6); hyperlipidemic, high-fat pig chow (H, n = 5); diabetic, standard pig chow (D, n = 7); diabetic, high-fat pig chow ("diabetic dyslipidemic," DD, n = 12); and exercise-trained DD (DDX, n = 9). High-fat chow consisted of standard minipig chow supplemented with cholesterol (2%) and coconut oil. Increased coronary vasoconstriction assessed in vivo and in vitro in DD was prevented by exercise. Patch-clamp experiments performed on right coronary artery smooth muscle cells resulted in greater K+ current densities in the H, D, and DD groups vs. the DDX group between -10 and 40 mV. In fura 2-loaded cells, current activated by caffeine-induced Ca2+ release was greater in H, D, and DD compared with C and DDX (P <0.05), whereas intracellular Ca 2+ concentration was not different across groups. Finally, there were no differences in the KCa or Kv channel protein content between groups. These data indicate that hyperglycemia, hyperlipidemia, and diabetic dyslipidemia lead to elevated whole cell K+ current and increased functional coupling of KCa and Ca2+ release. Endurance exercise prevented increased coupling of Ca2+ release to KCa channel activation in diabetic dyslipidemia.

Original languageEnglish (US)
Pages (from-to)1179-1193
Number of pages15
JournalJournal of Applied Physiology
Volume95
Issue number3
StatePublished - Sep 1 2003
Externally publishedYes

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Dichlorodiphenyl Dichloroethylene
Swine
Dyslipidemias
Hyperglycemia
Miniature Swine
Fats
Hyperlipidemias
Fura-2
Hypercholesterolemia
Caffeine
Vasoconstriction
Vascular Smooth Muscle
Smooth Muscle Myocytes
Coronary Vessels
Cholesterol
Exercise
Control Groups
Proteins

Keywords

  • Ca release
  • Ca-dependent K channel
  • Dyslipidemia
  • Porcine
  • Sarcoplasmic reticulum
  • Vascular smooth muscle
  • Voltage clamp

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise. / Mokelke, E. A.; Hu, Q.; Song, M.; Toro, L.; Reddy, H. K.; Sturek, Michael.

In: Journal of Applied Physiology, Vol. 95, No. 3, 01.09.2003, p. 1179-1193.

Research output: Contribution to journalArticle

Mokelke, E. A. ; Hu, Q. ; Song, M. ; Toro, L. ; Reddy, H. K. ; Sturek, Michael. / Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise. In: Journal of Applied Physiology. 2003 ; Vol. 95, No. 3. pp. 1179-1193.
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AU - Hu, Q.

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AU - Reddy, H. K.

AU - Sturek, Michael

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AB - Chronic hyperglycemia and hypercholesterolemia have been shown to alter ionic currents in vascular smooth muscle. We tested the hypothesis that the combined effect of hyperglycemia and hyperlipidemia (diabetic dyslipidemia) would increase the Ca2+-sensitive K+ (KCa) current as a compensatory response to an increase in intracellular Ca 2+ concentration. We also hypothesized that exercise training would prevent this elevation in KCa current. Miniature Yucatan swine were randomly assigned to five groups: control, standard pig chow (C, n = 6); hyperlipidemic, high-fat pig chow (H, n = 5); diabetic, standard pig chow (D, n = 7); diabetic, high-fat pig chow ("diabetic dyslipidemic," DD, n = 12); and exercise-trained DD (DDX, n = 9). High-fat chow consisted of standard minipig chow supplemented with cholesterol (2%) and coconut oil. Increased coronary vasoconstriction assessed in vivo and in vitro in DD was prevented by exercise. Patch-clamp experiments performed on right coronary artery smooth muscle cells resulted in greater K+ current densities in the H, D, and DD groups vs. the DDX group between -10 and 40 mV. In fura 2-loaded cells, current activated by caffeine-induced Ca2+ release was greater in H, D, and DD compared with C and DDX (P <0.05), whereas intracellular Ca 2+ concentration was not different across groups. Finally, there were no differences in the KCa or Kv channel protein content between groups. These data indicate that hyperglycemia, hyperlipidemia, and diabetic dyslipidemia lead to elevated whole cell K+ current and increased functional coupling of KCa and Ca2+ release. Endurance exercise prevented increased coupling of Ca2+ release to KCa channel activation in diabetic dyslipidemia.

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